Latin America: the Answer to Drug Companies' Problems?

It never seems to end. Once again, U.S. researchers are proposing a study in developing countries in which poor people would receive placebos instead of proven, lifesaving therapies. And this time, the U.S. government, in the form of the Food and Drug Administration (FDA), is playing a leading role.

In April 1997, Public Citizen blew the whistle on a set of 15 research studies involving HIV-positive pregnant women in which some of the women were not given AZT, a drug that had been shown to reduce dramatically the transmission of HIV from mother to infant (Health Letter Vol. 14, No. 5). Instead of AZT, thousands of women were given inactive drugs called placebos. Our criticism of those studies on ethical grounds unleashed an international storm that has yet to abate; in fact, the storm has just struck a new front.

The HIV trials resulted in an attempt by the research industry to greatly weaken the World Medical Association's (WMA) Declaration of Helsinki (Health Letter, Vol. 15, No. 5). However, at its annual meeting in Edinburgh, Scotland in October 2000, the WMA settled upon the following language: "The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods." The WMA also explicitly rejected the notion that researchers can provide inferior care in poorer countries.

While the researchers in the HIV studies were generally government scientists or academics who were apparently committed to helping residents of the developing world, the new wave of unethical research involves the for-profit pharmaceutical industry whose motives are far less clear. Seizing upon some of the same justifications put forth by the HIV researchers ("they wouldn't have been treated anyway"), drug companies are now invading the Third World with intent to conduct research that would be clearly unethical in the U.S. The number of foreign investigators registered with the FDA grew over five-fold in the decade of the 1990s.

The latest scandal involves a biotech startup company in Doylestown, PA called Discovery Laboratories, which, in collaboration with Johnson & Johnson, manufactures an experimental drug called Surfaxin for the treatment of the often-fatal Respiratory Distress Syndrome (RDS) in premature infants. The drug belongs to a class called surfactants, which are naturally occurring compounds that help the lungs to inflate. When given to premature infants, mortality is reduced by 34 percent. There are four approved surfactants on the U.S. market, selling at $1,100-$2,400 per course of treatment.

Discovery Laboratories is eager to market its drug in the U.S. because 40 percent of world-wide pharmaceutical sales occur in North America. But the company seeks to include a placebo arm in the study. One reason for this is that it is easier for the company to demonstrate that its product is better than nothing than to show that it is on a par with known effective drugs.

The company must also be well aware that the FDA has a long-standing love affair with inappropriate placebo-controlled trials. Because European regulators are more likely to accept studies in which the new drug is compared to a known effective drug (without a placebo group) as evidence of efficacy, FDA officials have been trying to persuade them to require placebo controls more often.

But, as the FDA readily admits, "Conduct of a placebo-controlled surfactant trial for premature infants with RDS is considered unethical in the USA." Indeed, the company is planning a study in Europe in which its drug is compared to an already approved surfactant, without a placebo group.

This is where the developing world comes in. The company has planned a placebo-controlled trial in Mexico, Bolivia, Peru and Ecuador, ensuring that at least a dozen infants in the placebo arm will die unnecessarily. And these wouldn't be just any Latin American infants; the company and the FDA admit that some hospitals in these countries use surfactants, so the plan is to conduct the experiment in those hospitals that don't-the race to the ethical bottom.

The FDA is currently considering whether to endorse this trial design, an endorsement the company craves if it is to gain access to the lucrative U.S. market. The issue was raised at an internal FDA meeting in late January with the all-too-revealing title: "Use of placebo-controls in life threatening diseases: is the developing world the answer?"

Public Citizen is concerned that this is just the beginning of a new trend in which the poverty of developing countries is used by drug companies and potentially the FDA to justify the provision of substandard medical care to their research subjects. The line in the sand must be drawn now.